{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:18:04Z","timestamp":1794003484538,"version":"4.8.0"},"reference-count":116,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.molmet.2025.102228","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T08:13:36Z","timestamp":1754468016000},"page":"102228","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"special_numbering":"C","title":["Three-dimensional network of creatine metabolism: From intracellular energy shuttle to systemic metabolic regulatory switch"],"prefix":"10.1016","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5037-6080","authenticated-orcid":false,"given":"Yuhui","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.molmet.2025.102228_bib1","doi-asserted-by":"crossref","first-page":"84881941","DOI":"10.3390\/nu14050921","article-title":"Effects of creatine supplementation on brain function and health","volume":"14","author":"Forbes","year":"2022","journal-title":"Nutrients"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2018.11.002","article-title":"New advances in adaptive thermogenesis: UCP1 and beyond","volume":"29","author":"Chouchani","year":"2019","journal-title":"Cell Metab"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib3","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/s42255-019-0035-x","article-title":"Ablation of adipocyte creatine transport impairs thermogenesis and causes diet-induced obesity","volume":"1","author":"Kazak","year":"2019","journal-title":"Nat Metab"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib4","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.cmet.2024.01.001","article-title":"Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB","volume":"36","author":"Rahbani","year":"2024","journal-title":"Cell Metab"},{"issue":"7846","key":"10.1016\/j.molmet.2025.102228_bib5","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/s41586-021-03221-y","article-title":"Creatine kinase B controls futile creatine cycling in thermogenic fat","volume":"590","author":"Rahbani","year":"2021","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib6","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1042\/bj0210190","article-title":"The inorganic phosphate and a labile form of organic phosphate in the gastrocnemius of the frog","volume":"21","author":"Eggleton","year":"1927","journal-title":"Biochem J"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib7","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1113\/jphysiol.1933.sp003043","article-title":"The influence of the parathyroid on the metabolism of creatine and phosphoric acid","volume":"79","author":"Imrie","year":"1933","journal-title":"J Physiol"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0021-9258(18)65434-1","article-title":"Adenosinetriphosphate-creatine transphosphorylase. IV. Equilibrium studies","volume":"210","author":"Noda","year":"1954","journal-title":"J Biol Chem"},{"issue":"5","key":"10.1016\/j.molmet.2025.102228_bib9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/0006-291X(66)90317-2","article-title":"The possible role of the mitochondrial bound creatine kinase in regulation of mitochondrial respiration","volume":"22","author":"Bessman","year":"1966","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib10","first-page":"151","article-title":"Skeletal muscle function and structure after depletion of creatine","volume":"33","author":"Shields","year":"1975","journal-title":"Lab Invest"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib11","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1093\/cvr\/11.3.250","article-title":"Subcellular compartmentation of creatine kinase isoenzymes in Guinea pig heart","volume":"11","author":"Ogunro","year":"1977","journal-title":"Cardiovasc Res"},{"issue":"6","key":"10.1016\/j.molmet.2025.102228_bib12","first-page":"583","article-title":"The hypodynamic state of the frog heart. Further evidence for a phosphocreatine-creatine pathway","volume":"76","author":"Ventura-Clapier","year":"1980","journal-title":"J Physiol (Paris)"},{"issue":"4481","key":"10.1016\/j.molmet.2025.102228_bib13","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1126\/science.6450446","article-title":"Transport of energy in muscle: the phosphorylcreatine shuttle","volume":"211","author":"Bessman","year":"1981","journal-title":"Science"},{"issue":"5 Pt 1","key":"10.1016\/j.molmet.2025.102228_bib14","doi-asserted-by":"crossref","first-page":"C365","DOI":"10.1152\/ajpcell.1984.246.5.C365","article-title":"A simple analysis of the \u201cphosphocreatine shuttle\u201d","volume":"246","author":"Meyer","year":"1984","journal-title":"Am J Physiol"},{"issue":"3 Pt 1","key":"10.1016\/j.molmet.2025.102228_bib15","doi-asserted-by":"crossref","first-page":"C279","DOI":"10.1152\/ajpcell.1985.248.3.C279","article-title":"Phosphorus nuclear magnetic resonance of fast- and slow-twitch muscle","volume":"248","author":"Meyer","year":"1985","journal-title":"Am J Physiol"},{"issue":"Pt 1","key":"10.1016\/j.molmet.2025.102228_bib16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/bj2810021","article-title":"Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the \u2018phosphocreatine circuit\u2019 for cellular energy homeostasis","volume":"281","author":"Wallimann","year":"1992","journal-title":"Biochem J"},{"key":"10.1016\/j.molmet.2025.102228_bib17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/BF01267954","article-title":"Metabolic compartmentation and substrate channelling in muscle cells. Role of coupled creatine kinases in in vivo regulation of cellular respiration--a synthesis","volume":"133\u2013134","author":"Saks","year":"1994","journal-title":"Mol Cell Biochem"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0171-9335(98)80096-4","article-title":"The isoenzyme-diagnostic regions of muscle-type creatine kinase, the M-260 and M-300 box, are not responsible for its binding to the myofibrillar M-band","volume":"77","author":"Stolz","year":"1998","journal-title":"Eur J Cell Biol"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib19","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0005-2728(93)90200-Y","article-title":"Quantitative analysis of the \u2018phosphocreatine shuttle\u2019: I. A probability approach to the description of phosphocreatine production in the coupled creatine kinase-ATP\/ADP translocase-oxidative phosphorylation reactions in heart mitochondria","volume":"1143","author":"Aliev","year":"1993","journal-title":"Biochim Biophys Acta"},{"issue":"Pt 3","key":"10.1016\/j.molmet.2025.102228_bib20","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1113\/jphysiol.2001.012858","article-title":"The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle","volume":"537","author":"Walsh","year":"2001","journal-title":"J Physiol"},{"issue":"1\u20132","key":"10.1016\/j.molmet.2025.102228_bib21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1023\/A:1007002323492","article-title":"Developmental changes in regulation of mitochondrial respiration by ADP and creatine in rat heart in vivo","volume":"208","author":"Tiivel","year":"2000","journal-title":"Mol Cell Biochem"},{"issue":"Pt 1","key":"10.1016\/j.molmet.2025.102228_bib22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1113\/jphysiol.2006.114116","article-title":"Altered energy transfer from mitochondria to sarcoplasmic reticulum after cytoarchitectural perturbations in mice hearts","volume":"575","author":"Wilding","year":"2006","journal-title":"J Physiol"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib23","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0005-2728(96)00074-6","article-title":"Differential effects of creatine depletion on the regulation of enzyme activities and on creatine-stimulated mitochondrial respiration in skeletal muscle, heart, and brain","volume":"1276","author":"O\u2019Gorman","year":"1996","journal-title":"Biochim Biophys Acta"},{"issue":"9","key":"10.1016\/j.molmet.2025.102228_bib24","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.bbabio.2009.03.024","article-title":"Regulation of respiration controlled by mitochondrial creatine kinase in permeabilized cardiac cells in situ. Importance of system level properties","volume":"1787","author":"Guzun","year":"2009","journal-title":"Biochim Biophys Acta"},{"issue":"23","key":"10.1016\/j.molmet.2025.102228_bib25","doi-asserted-by":"crossref","first-page":"24334","DOI":"10.1074\/jbc.M314158200","article-title":"C-terminal lysines determine phospholipid interaction of sarcomeric mitochondrial creatine kinase","volume":"279","author":"Schlattner","year":"2004","journal-title":"J Biol Chem"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib26","doi-asserted-by":"crossref","first-page":"219","DOI":"10.4149\/gpb_2009_03_219","article-title":"Architectural and functional remodeling of cardiac and skeletal muscle cells in mice lacking specific isoenzymes of creatine kinase","volume":"28","author":"Tylkova","year":"2009","journal-title":"Gen Physiol Biophys"},{"issue":"Pt 21","key":"10.1016\/j.molmet.2025.102228_bib27","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1113\/jphysiol.2011.212829","article-title":"Rearrangement of energetic and substrate utilization networks compensate for chronic myocardial creatine kinase deficiency","volume":"589","author":"Dzeja","year":"2011","journal-title":"J Physiol"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib28","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.cell.2015.09.035","article-title":"A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat","volume":"163","author":"Kazak","year":"2015","journal-title":"Cell"},{"issue":"4","key":"10.1016\/j.molmet.2025.102228_bib29","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.cmet.2017.08.009","article-title":"Genetic depletion of adipocyte creatine metabolism inhibits diet-induced thermogenesis and drives obesity","volume":"26","author":"Kazak","year":"2017","journal-title":"Cell Metab"},{"issue":"10","key":"10.1016\/j.molmet.2025.102228_bib30","doi-asserted-by":"crossref","first-page":"4147","DOI":"10.1096\/fj.12-225136","article-title":"Differential regulation of AMPK activation in leptin- and creatine-deficient mice","volume":"27","author":"Stockebrand","year":"2013","journal-title":"FASEB J"},{"issue":"8","key":"10.1016\/j.molmet.2025.102228_bib31","doi-asserted-by":"crossref","DOI":"10.3390\/nu13082758","article-title":"Creatine supplementation upregulates mTORC1 signaling and markers of synaptic plasticity in the dentate gyrus while ameliorating LPS-induced cognitive impairment in female rats","volume":"13","author":"Mao","year":"2021","journal-title":"Nutrients"},{"key":"10.1016\/j.molmet.2025.102228_bib32","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.biochi.2023.02.004","article-title":"Creatine ameliorates high-fat diet-induced obesity by regulation of lipolysis and lipophagy in brown adipose tissue and liver","volume":"209","author":"Chen","year":"2023","journal-title":"Biochimie"},{"key":"10.1016\/j.molmet.2025.102228_bib33","doi-asserted-by":"crossref","first-page":"121064","DOI":"10.1016\/j.lfs.2022.121064","article-title":"Creatine supplementation protects against diet-induced non-alcoholic fatty liver but exacerbates alcoholic fatty liver","volume":"310","author":"Marinello","year":"2022","journal-title":"Life Sci"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib34","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.bbrc.2015.07.034","article-title":"Mitochondrial ATP synthasome: expression and structural interaction of its components","volume":"464","author":"Nuskova","year":"2015","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib35","doi-asserted-by":"crossref","first-page":"11528","DOI":"10.1038\/s41598-018-29972-9","article-title":"The metabolomic bioenergetic signature of Opa1-disrupted mouse embryonic fibroblasts highlights aspartate deficiency","volume":"8","author":"Bocca","year":"2018","journal-title":"Sci Rep"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib36","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s42255-022-00718-2","article-title":"A critical assessment of the role of creatine in brown adipose tissue thermogenesis","volume":"5","author":"Nicholls","year":"2023","journal-title":"Nat Metab"},{"issue":"49","key":"10.1016\/j.molmet.2025.102228_bib37","doi-asserted-by":"crossref","first-page":"37361","DOI":"10.1074\/jbc.M604123200","article-title":"Mitochondrial creatine kinase activity prevents reactive oxygen species generation: antioxidant role of mitochondrial kinase-dependent ADP re-cycling activity","volume":"281","author":"Meyer","year":"2006","journal-title":"J Biol Chem"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib38","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.cmet.2021.01.018","article-title":"Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer","volume":"33","author":"Maguire","year":"2021","journal-title":"Cell Metab"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib39","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/jn\/nxab415","article-title":"Inverse association between hypothalamic N-acetyl aspartate\/creatine ratio and indices of body mass in adolescents with obesity","volume":"152","author":"Neves","year":"2022","journal-title":"J Nutr"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib40","doi-asserted-by":"crossref","first-page":"2441760","DOI":"10.1080\/15502783.2024.2441760","article-title":"Part II. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?","volume":"22","author":"Antonio","year":"2025","journal-title":"J Int Soc Sports Nutr"},{"key":"10.1016\/j.molmet.2025.102228_bib41","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.neuint.2015.08.010","article-title":"Creatine as a booster for human brain function. How might it work?","volume":"89","author":"Rae","year":"2015","journal-title":"Neurochem Int"},{"issue":"7818","key":"10.1016\/j.molmet.2025.102228_bib42","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/s41586-020-2527-y","article-title":"A leptin-BDNF pathway regulating sympathetic innervation of adipose tissue","volume":"583","author":"Wang","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.molmet.2025.102228_bib43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2023.02.011","article-title":"Body fat and components of sarcopenia relate to inflammation, brain volume, and neurometabolism in older adults","volume":"127","author":"Vints","year":"2023","journal-title":"Neurobiol Aging"},{"issue":"Suppl 1","key":"10.1016\/j.molmet.2025.102228_bib44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s40279-023-01870-9","article-title":"\"Heads up\u201d for creatine supplementation and its potential applications for brain health and function","volume":"53","author":"Candow","year":"2023","journal-title":"Sports Med"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/17461391.2018.1500644","article-title":"Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury","volume":"19","author":"Dolan","year":"2019","journal-title":"Eur J Sport Sci"},{"issue":"6","key":"10.1016\/j.molmet.2025.102228_bib46","doi-asserted-by":"crossref","DOI":"10.1152\/japplphysiol.01327.2006","article-title":"Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy","volume":"102","author":"Kan","year":"1985","journal-title":"J Appl Physiol"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib47","doi-asserted-by":"crossref","first-page":"E256","DOI":"10.1152\/ajpendo.90547.2008","article-title":"Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo","volume":"296","author":"Da","year":"2009","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"10.1016\/j.molmet.2025.102228_bib48","doi-asserted-by":"crossref","first-page":"1230457","DOI":"10.3389\/fendo.2023.1230457","article-title":"Serum metabolomic profiling unveils distinct sex-related metabolic patterns in NAFLD","volume":"14","author":"Fotakis","year":"2023","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.molmet.2025.102228_bib49","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jnutbio.2017.08.010","article-title":"Dietary creatine supplementation lowers hepatic triacylglycerol by increasing lipoprotein secretion in rats fed high-fat diet","volume":"50","author":"Da","year":"2017","journal-title":"J Nutr Biochem"},{"issue":"4","key":"10.1016\/j.molmet.2025.102228_bib50","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1002\/fsn3.3201","article-title":"Guanidinoacetic acid in human nutrition: beyond creatine synthesis","volume":"11","author":"Ostojic","year":"2023","journal-title":"Food Sci Nutr"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib51","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jmb.2007.04.073","article-title":"The supramolecular assemblies of voltage-dependent anion channels in the native membrane","volume":"370","author":"Hoogenboom","year":"2007","journal-title":"J Mol Biol"},{"issue":"51","key":"10.1016\/j.molmet.2025.102228_bib52","doi-asserted-by":"crossref","first-page":"9246","DOI":"10.1021\/bi4011495","article-title":"ATP transport through VDAC and the VDAC-tubulin complex probed by equilibrium and nonequilibrium MD simulations","volume":"52","author":"Noskov","year":"2013","journal-title":"Biochemistry"},{"issue":"18","key":"10.1016\/j.molmet.2025.102228_bib53","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1042\/BCJ20160373","article-title":"In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport","volume":"473","author":"Miotto","year":"2016","journal-title":"Biochem J"},{"issue":"4","key":"10.1016\/j.molmet.2025.102228_bib54","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cmet.2017.03.002","article-title":"Mitochondrial patch clamp of beige adipocytes reveals UCP1-positive and UCP1-negative cells both exhibiting futile creatine cycling","volume":"25","author":"Bertholet","year":"2017","journal-title":"Cell Metab"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib55","article-title":"Ucp1 ablation improves skeletal muscle glycolytic function in aging mice","volume":"12","author":"Qiu","year":"2025","journal-title":"Adv Sci (Weinh)"},{"issue":"7","key":"10.1016\/j.molmet.2025.102228_bib56","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41574-021-00513-1","article-title":"Unravelling the molecular basis of futile creatine cycling","volume":"17","author":"Greenhill","year":"2021","journal-title":"Nat Rev Endocrinol"},{"key":"10.1016\/j.molmet.2025.102228_bib57","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-0716-2087-8_10","article-title":"Measurement of futile creatine cycling using respirometry","volume":"2448","author":"Rahbani","year":"2022","journal-title":"Methods Mol Biol"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib58","doi-asserted-by":"crossref","DOI":"10.3390\/biom10020320","article-title":"Regulation of Nrf2 by mitochondrial reactive oxygen species in Physiology and pathology","volume":"10","author":"Kasai","year":"2020","journal-title":"Biomolecules"},{"issue":"11","key":"10.1016\/j.molmet.2025.102228_bib59","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/s42255-022-00667-w","article-title":"ADRA1A-Galpha(q) signalling potentiates adipocyte thermogenesis through CKB and TNAP","volume":"4","author":"Rahbani","year":"2022","journal-title":"Nat Metab"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib60","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1038\/s41467-025-58294-4","article-title":"The Futile Creatine Cycle powers UCP1-independent thermogenesis in classical BAT","volume":"16","author":"Bunk","year":"2025","journal-title":"Nat Commun"},{"issue":"6","key":"10.1016\/j.molmet.2025.102228_bib61","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.bbamem.2011.12.034","article-title":"Regulation of respiration in muscle cells in vivo by VDAC through interaction with the cytoskeleton and MtCK within Mitochondrial Interactosome","volume":"1818","author":"Guzun","year":"2012","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib62","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1111\/tbed.13783","article-title":"Ancient origin and genetic segregation of canine circovirus infecting arctic foxes (Vulpes lagopus) in Svalbard and red foxes (Vulpes vulpes) in Northern Norway","volume":"68","author":"Urbani","year":"2021","journal-title":"Transbound Emerg Dis"},{"key":"10.1016\/j.molmet.2025.102228_bib63","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/978-981-10-7757-9_13","article-title":"Mitochondrial proteolipid complexes of creatine kinase","volume":"87","author":"Schlattner","year":"2018","journal-title":"Subcell Biochem"},{"issue":"23","key":"10.1016\/j.molmet.2025.102228_bib64","doi-asserted-by":"crossref","first-page":"17314","DOI":"10.1074\/jbc.M001919200","article-title":"Octamers of mitochondrial creatine kinase isoenzymes differ in stability and membrane binding","volume":"275","author":"Schlattner","year":"2000","journal-title":"J Biol Chem"},{"issue":"1\u20132","key":"10.1016\/j.molmet.2025.102228_bib65","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.gene.2008.04.003","article-title":"Identification, characterization and cloning of SLC6A8C, a novel splice variant of the creatine transporter gene","volume":"418","author":"Martinez-Munoz","year":"2008","journal-title":"Gene"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib66","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1186\/s12864-019-6361-2","article-title":"Parallel selection on ecologically relevant gene functions in the transcriptomes of highly diversifying salmonids","volume":"20","author":"Schneider","year":"2019","journal-title":"BMC Genom"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib67","doi-asserted-by":"crossref","first-page":"7303","DOI":"10.1038\/s41467-022-34964-5","article-title":"Epigenetic regulation of white adipose tissue plasticity and energy metabolism by nucleosome binding HMGN proteins","volume":"13","author":"Nanduri","year":"2022","journal-title":"Nat Commun"},{"key":"10.1016\/j.molmet.2025.102228_bib68","doi-asserted-by":"crossref","first-page":"117838","DOI":"10.1016\/j.biopha.2025.117838","article-title":"Compound K promotes thermogenic signature and mitochondrial biogenesis via the UCP1-SIRT3-PGC1alpha signaling pathway","volume":"183","author":"Oh","year":"2025","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.molmet.2025.102228_bib69","doi-asserted-by":"crossref","first-page":"102082","DOI":"10.1016\/j.molmet.2024.102082","article-title":"Epigenetic suppression of creatine kinase B in adipocytes links endoplasmic reticulum stress to obesity-associated inflammation","volume":"92","author":"Renzi","year":"2025","journal-title":"Mol Metabol"},{"issue":"768","key":"10.1016\/j.molmet.2025.102228_bib70","doi-asserted-by":"crossref","first-page":"eado3022","DOI":"10.1126\/scitranslmed.ado3022","article-title":"Decreased mitochondrial creatine kinase 2 impairs skeletal muscle mitochondrial function independently of insulin in type 2 diabetes","volume":"16","author":"Rizo-Roca","year":"2024","journal-title":"Sci Transl Med"},{"issue":"5","key":"10.1016\/j.molmet.2025.102228_bib71","doi-asserted-by":"crossref","first-page":"zqac037","DOI":"10.1093\/function\/zqac037","article-title":"Ckmt1 is dispensable for mitochondrial bioenergetics within white\/beige adipose tissue","volume":"3","author":"Politis-Barber","year":"2022","journal-title":"Function (Oxf)"},{"key":"10.1016\/j.molmet.2025.102228_bib72","doi-asserted-by":"crossref","DOI":"10.1038\/s42255-025-01311-z","article-title":"A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss","author":"Cal","year":"2025","journal-title":"Nat Metab"},{"issue":"5","key":"10.1016\/j.molmet.2025.102228_bib73","article-title":"beta-GPA treatment leads to elevated basal metabolic rate and enhanced hypoxic exercise tolerance in mice","volume":"5","author":"Ross","year":"2017","journal-title":"Phys Rep"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib74","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s42255-020-00337-9","article-title":"Creatine supplementation and thermogenesis in humans-a futile exercise?","volume":"3","author":"Modica","year":"2021","journal-title":"Nat Metab"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib75","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s42255-020-00332-0","article-title":"No evidence for brown adipose tissue activation after creatine supplementation in adult vegetarians","volume":"3","author":"Connell","year":"2021","journal-title":"Nat Metab"},{"issue":"11","key":"10.1016\/j.molmet.2025.102228_bib76","doi-asserted-by":"crossref","DOI":"10.3390\/nu13113985","article-title":"Effects of low doses of L-carnitine tartrate and lipid multi-particulate formulated creatine monohydrate on muscle protein synthesis in myoblasts and bioavailability in humans and rodents","volume":"13","author":"Fielding","year":"2021","journal-title":"Nutrients"},{"issue":"6","key":"10.1016\/j.molmet.2025.102228_bib77","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1093\/cvr\/cvy054","article-title":"Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion","volume":"114","author":"Whittington","year":"2018","journal-title":"Cardiovasc Res"},{"issue":"4","key":"10.1016\/j.molmet.2025.102228_bib78","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/evan.21894","article-title":"Between a rock and a cold place: Neanderthal biocultural cold adaptations","volume":"30","author":"Ocobock","year":"2021","journal-title":"Evol Anthropol"},{"key":"10.1016\/j.molmet.2025.102228_bib79","doi-asserted-by":"crossref","first-page":"1128133","DOI":"10.3389\/fgene.2023.1128133","article-title":"Genetic variants in genes involved in creatine biosynthesis in patients with severe obesity or anorexia nervosa","volume":"14","author":"Rajcsanyi","year":"2023","journal-title":"Front Genet"},{"issue":"4","key":"10.1016\/j.molmet.2025.102228_bib80","doi-asserted-by":"crossref","first-page":"110290","DOI":"10.1016\/j.celrep.2021.110290","article-title":"Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth","volume":"38","author":"Rampelt","year":"2022","journal-title":"Cell Rep"},{"issue":"8","key":"10.1016\/j.molmet.2025.102228_bib81","doi-asserted-by":"crossref","first-page":"148430","DOI":"10.1016\/j.bbabio.2021.148430","article-title":"Oxidative phosphorylation K(0.5)ADP in vitro depends on substrate oxidative capacity: insights from a luciferase-based assay to evaluate ADP kinetic parameters","volume":"1862","author":"Willis","year":"2021","journal-title":"Biochim Biophys Acta Bioenerg"},{"issue":"7","key":"10.1016\/j.molmet.2025.102228_bib82","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.tcb.2023.10.004","article-title":"Mitochondrial complexome and import network","volume":"34","author":"den Brave","year":"2024","journal-title":"Trends Cell Biol"},{"issue":"7","key":"10.1016\/j.molmet.2025.102228_bib83","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.bbamem.2014.02.007","article-title":"VDAC electronics: 2. A new, anaerobic mechanism of generation of the membrane potentials in mitochondria","volume":"1838","author":"Lemeshko","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"12","key":"10.1016\/j.molmet.2025.102228_bib84","doi-asserted-by":"crossref","first-page":"4147","DOI":"10.1002\/chem.201504428","article-title":"Stereopositional outcome in the packing of dissimilar aromatics in designed beta-hairpins","volume":"22","author":"Makwana","year":"2016","journal-title":"Chemistry"},{"issue":"11","key":"10.1016\/j.molmet.2025.102228_bib85","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1113\/JP271259","article-title":"Modelling in vivo creatine\/phosphocreatine in vitro reveals divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise","volume":"594","author":"Ydfors","year":"2016","journal-title":"J Physiol"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib86","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1042\/BJ20110366","article-title":"Inhibiting myosin-ATPase reveals a dynamic range of mitochondrial respiratory control in skeletal muscle","volume":"437","author":"Perry","year":"2011","journal-title":"Biochem J"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib87","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jmr.2004.08.015","article-title":"Molecular dynamics and information on possible sites of interaction of intramyocellular metabolites in vivo from resolved dipolar couplings in localized 1H NMR spectra","volume":"171","author":"Schroder","year":"2004","journal-title":"J Magn Reson"},{"issue":"48","key":"10.1016\/j.molmet.2025.102228_bib88","doi-asserted-by":"crossref","first-page":"34684","DOI":"10.1074\/jbc.M707231200","article-title":"Inhibition of human dimethylarginine dimethylaminohydrolase-1 by S-nitroso-L-homocysteine and hydrogen peroxide. Analysis, quantification, and implications for hyperhomocysteinemia","volume":"282","author":"Hong","year":"2007","journal-title":"J Biol Chem"},{"issue":"18","key":"10.1016\/j.molmet.2025.102228_bib89","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1042\/BCJ20160373","article-title":"In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport","volume":"473","author":"Miotto","year":"2016","journal-title":"Biochem J"},{"issue":"7","key":"10.1016\/j.molmet.2025.102228_bib90","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.bbamem.2014.02.007","article-title":"VDAC electronics: 2. A new, anaerobic mechanism of generation of the membrane potentials in mitochondria","volume":"1838","author":"Lemeshko","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib91","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1124\/jpet.109.153213","article-title":"Mitochondrial permeability transition pore opening as a promising therapeutic target in cardiac diseases","volume":"330","author":"Javadov","year":"2009","journal-title":"J Pharmacol Exp Therapeut"},{"issue":"16","key":"10.1016\/j.molmet.2025.102228_bib92","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.2174\/0929867033457278","article-title":"The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death","volume":"10","author":"Halestrap","year":"2003","journal-title":"Curr Med Chem"},{"key":"10.1016\/j.molmet.2025.102228_bib93","doi-asserted-by":"crossref","unstructured":"Sharma S, Belluati A, Kumar M, Dhiman S, Enzymatic reaction network-driven polymerization-induced transient coacervation. Angew Chem Int Ed Engl 2024;6411:e202421620.","DOI":"10.1002\/anie.202421620"},{"issue":"21","key":"10.1016\/j.molmet.2025.102228_bib94","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1002\/1873-3468.14994","article-title":"Compartmentalization in cardiomyocytes modulates creatine kinase and adenylate kinase activities","volume":"598","author":"Birkedal","year":"2024","journal-title":"FEBS Lett"},{"issue":"8","key":"10.1016\/j.molmet.2025.102228_bib95","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.tcb.2022.11.009","article-title":"Kinase regulation by liquid-liquid phase separation","volume":"33","author":"Lopez-Palacios","year":"2023","journal-title":"Trends Cell Biol"},{"key":"10.1016\/j.molmet.2025.102228_bib96","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/852430","article-title":"Annexin A2 at the interface of actin and membrane dynamics: a focus on its roles in endocytosis and cell polarization","volume":"2012","author":"Grieve","year":"2012","journal-title":"Int J Cell Biol"},{"issue":"7","key":"10.1016\/j.molmet.2025.102228_bib97","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/pro.4079","article-title":"Adenosine triphosphate energy-independently controls protein homeostasis with unique structure and diverse mechanisms","volume":"30","author":"Song","year":"2021","journal-title":"Protein Sci"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib98","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1038\/s41467-022-32889-7","article-title":"Spatiotemporal control of signal-driven enzymatic reaction in artificial cell-like polymersomes","volume":"13","author":"Seo","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib99","doi-asserted-by":"crossref","first-page":"R392","DOI":"10.1152\/ajpregu.00056.2007","article-title":"Influence of endurance training on muscle [PCr] kinetics during high-intensity exercise","volume":"293","author":"Jones","year":"2007","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"10.1016\/j.molmet.2025.102228_bib100","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2023.1155521","article-title":"Reversible protein assemblies in the proteostasis network in health and disease","volume":"10","author":"Kohler","year":"2023","journal-title":"Front Mol Biosci"},{"key":"10.1016\/j.molmet.2025.102228_bib101","doi-asserted-by":"crossref","first-page":"110083","DOI":"10.1016\/j.neuropharm.2024.110083","article-title":"Implications of liquid-liquid phase separation and ferroptosis in Alzheimer\u2019s disease","volume":"259","author":"Wang","year":"2024","journal-title":"Neuropharmacology"},{"issue":"2","key":"10.1016\/j.molmet.2025.102228_bib102","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1042\/BJ20102007","article-title":"Slow skeletal muscle myosin-binding protein-C (MyBPC1) mediates recruitment of muscle-type creatine kinase (CK) to myosin","volume":"436","author":"Chen","year":"2011","journal-title":"Biochem J"},{"issue":"4","key":"10.1016\/j.molmet.2025.102228_bib103","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.cbpa.2008.04.604","article-title":"Dependence of myosin-ATPase on structure bound creatine kinase in cardiac myofibrils from rainbow trout and freshwater turtle","volume":"150","author":"Haagensen","year":"2008","journal-title":"Comp Biochem Physiol Mol Integr Physiol"},{"key":"10.1016\/j.molmet.2025.102228_bib104","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.bbagen.2017.02.001","article-title":"Evidence of proteolipid domain formation in an inner mitochondrial membrane mimicking model","volume":"1861(5 Pt A)","author":"Cheniour","year":"2017","journal-title":"Biochim Biophys Acta Gen Subj"},{"issue":"1","key":"10.1016\/j.molmet.2025.102228_bib105","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1038\/s41467-022-30506-1","article-title":"Cryo-EM structures define ubiquinone-10 binding to mitochondrial complex I and conformational transitions accompanying Q-site occupancy","volume":"13","author":"Chung","year":"2022","journal-title":"Nat Commun"},{"issue":"6","key":"10.1016\/j.molmet.2025.102228_bib106","doi-asserted-by":"crossref","DOI":"10.3390\/nu14061230","article-title":"Low tissue creatine: a therapeutic target in clinical nutrition","volume":"14","author":"Ostojic","year":"2022","journal-title":"Nutrients"},{"issue":"11","key":"10.1016\/j.molmet.2025.102228_bib107","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/nrendo.2017.120","article-title":"Obesity: role for creatine metabolism in energy expenditure","volume":"13","author":"Greenhill","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"10.1016\/j.molmet.2025.102228_bib108","doi-asserted-by":"crossref","first-page":"119726","DOI":"10.1016\/j.cca.2024.119726","article-title":"Creatine kinase serum levels in children revisited: new reference intervals from a large cohort of healthy children and adolescents","volume":"560","author":"Fechner","year":"2024","journal-title":"Clin Chim Acta"},{"issue":"19","key":"10.1016\/j.molmet.2025.102228_bib109","doi-asserted-by":"crossref","DOI":"10.3390\/cells11193023","article-title":"Liquid-liquid phase separation of biomacromolecules and its roles in metabolic diseases","volume":"11","author":"Chen","year":"2022","journal-title":"Cells"},{"issue":"6","key":"10.1016\/j.molmet.2025.102228_bib110","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.biochi.2009.03.014","article-title":"Mitochondrial creatine kinase interaction with heterogeneous monolayers: effect on lipid lateral organization","volume":"91","author":"Vernoux","year":"2009","journal-title":"Biochimie"},{"issue":"6","key":"10.1016\/j.molmet.2025.102228_bib111","doi-asserted-by":"crossref","DOI":"10.1093\/jmcb\/mjae018","article-title":"HSD17B13 liquid-liquid phase separation promotes leukocyte adhesion in chronic liver inflammation","volume":"16","author":"Ye","year":"2024","journal-title":"J Mol Cell Biol"},{"issue":"23","key":"10.1016\/j.molmet.2025.102228_bib112","article-title":"LncRNA-MEG3 regulates muscle mass and metabolic homeostasis by facilitating SUZ12 liquid-liquid phase separation","volume":"12","author":"Yao","year":"2025","journal-title":"Adv Sci (Weinh)"},{"issue":"5","key":"10.1016\/j.molmet.2025.102228_bib113","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.263433","article-title":"The non-canonical Smoothened-AMPK axis regulates Smaug1 biomolecular condensates","volume":"138","author":"Thomas","year":"2025","journal-title":"J Cell Sci"},{"issue":"12","key":"10.1016\/j.molmet.2025.102228_bib114","doi-asserted-by":"crossref","DOI":"10.3390\/biom14121517","article-title":"Molecular mechanisms underlying initiation and activation of autophagy","volume":"14","author":"Wei","year":"2024","journal-title":"Biomolecules"},{"issue":"3","key":"10.1016\/j.molmet.2025.102228_bib115","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0009-8981(85)90350-X","article-title":"Creatine kinase: purification, characterization, and tissue distribution of the MM subtypes","volume":"153","author":"Mickelson","year":"1985","journal-title":"Clin Chim Acta"},{"key":"10.1016\/j.molmet.2025.102228_bib116","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.msec.2017.04.053","article-title":"Designing structural features of novel benznidazole-loaded cationic nanoparticles for inducing slow drug release and improvement of biological efficacy","volume":"78","author":"Dos","year":"2017","journal-title":"Mater Sci Eng C Mater Biol Appl"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877825001358?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877825001358?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T23:01:57Z","timestamp":1758668517000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212877825001358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":116,"alternative-id":["S2212877825001358"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2025.102228","relation":{},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Three-dimensional network of creatine metabolism: From intracellular energy shuttle to systemic metabolic regulatory switch","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2025.102228","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"102228"}}